3-(beta-aryl-beta-(arylthio) (or arylseleno) propionyl)-coumarin products



United States Patent 3,489,774 3-(p-ARYL-p-(ARYLTHIO) (OR ARYLSELENO) PROPIONYL)-COUMARIN PRODUCTS Stephen J. Kuhn and John S. McIntyre, Sarnia, Ontario,

Canada, assignors to The Dow Chemical Company,

Midland, Mich., a corporation of Delaware No Drawing. Filed Apr. 24, 1967, Ser. No. 632,940

Int. Cl. C07d 7/00; A01n 9/24 US. Cl. 260343.2 4 Claims ABSTRACT OF THE DISCLOSURE The present invention is concerned with the addition of any arylthiol or arylselenol of the formula wherein R represents sulfur or selenium to a pyrone or coumarin compound of the formula to obtain novel 3-(B-aryl-fi-(arylthio)(or arylseleno)- propionyl)pyrone and coumarin products of the following formula:

In the above and succeeding formulae in the present specification and claims, R represents sulfur or selenium; R represents a phenyl radical of the formula wherein Z represents bromo, chloro, or loweralkyl of from 1 to 4, both inclusive, carbon atoms, and n represents 0 or 1; R" represents Z-thienyl, 9-phenanthryl, phenyl, or phenyl substituted by from 1 to 2 substituents, each of which is independently bromo, chloro, methyl, or methoxy; and R represents hydrogen and R" represents hydrogen, methyl, or phenyl, or R and R"", taken together, jointly represent a four-carbon-atom divalent radical which with the two carbon atoms upon which R" and R"" are substituents constitutes a siX-carbon-atom unsaturated ring.

The products of the present invention are useful as parasiticides, particularly as agents to control the growth of fungi and bacteria, such as Candida albicans, Bacillus subtilis, Aspergillus terreus, Pullularizz pululans, tomato late blight, Staphylococcus aureus, rice blast, and Trichophyton mentagrophytes; the products are also useful as herbicides for the control of weeds, such as bindweed and pigweed.

3,489,774 Patented Jan. 13, 1970 BACKGROUND OF THE INVENTION Certain compounds having the following type structure:

are known in the prior art.

SUMMARY OF THE INVENTION It has now been found that when such compounds:

As noted foregoing, these products are useful as parasiticides and as herbicides.

DESCRIPTION OF THE PREFERRED EMBODIMENTS The products of the present invention are prepared by causing the reaction of an arylthiol or arylselenol of the formula HRR' and a pyrone or coumarin compound of the formula:

OH O R 3CH=CHR" The reaction results in the preparation of the desired products of the formula In the above and succeeding formulae in the present specification and claims, R represents sulfur or selenium; R' represents a phenyl radical of the formula wherein Z represents bromo, chloro, or .loweralkyl of from 1 to 4, both inclusive, carbon atoms, and n represents Q or .1; RT. represents Z-thienyl, 9-phenanthryl, phenyl, or phenyl substituted by from 1 to Zsubstituents, each oij which is independently bromo, chloro, methyl, or methoxy; and R represents hydrogen and R"" represents hydrogen, methyl, or phenyl, or R'," and R'.",,tal en" together, jointly represent a four-,carbonratorn divalent radicalwhich with the two carbon atoms upon'which R' and Rf are substituents Constitutes a' six-'carbon-atom unsaturated ring.

Thereactionof arylthiol or aryls elenol and the pyrone or coumarin compound is'catalyzed by a small amount of an organic secondary amine, such as a dialkylamine or piperidine. The reaction is conveniently carried out in an inert liquid reaction medium. As such reaction medium, organic liquids are typically employed; hydrocarbons, alcohols, ethers, and halogenated alkanes are classes of organic liquids suitable for this purpose. The reaction goes forward under temperatures of a wide range, such as from room temperatures to 110 C., or higher. However, when catalyst is employed, less severe reaction conditions suffice and the reaction is conveniently and preferably conducted at temperatures of from 30 to 80 C., in the instance of a starting pyrone compound, and to 60 C. in the instance of a starting coumarin compound.

The amounts of the reactants employed are not critical, some of the desired product being obtained when employ ing the reactants in any amounts. However, the reaction consumes the reactants in amounts representing equi-molecular amounts, and the supplying of the reactants in such amounts avoids the deleterious effects of an excess amount of either reactant and is accordingly preferred. A minor amount of the secondary amine catalyst is sufficient to catalyze the reaction. The best reactant mole ratio has been found to be 1:1:0.01 (pyrone or coumarinzarylthiol or arylselenolzamine).

In carrying out the reaction, the reactants are contacted with one another in the reaction temperature range, conveniently in reaction medium, as discussed above, and preferably in the presence of acatalytic amount of secondary amine. Speed of the reaction is dependent upon the conditions under which it is carried out. When no catalyst is employed, several hours may be required to obtain high yields; when catalyst is used, reaction times of several minutes or less to one-half hour are generally sufiicient. The reaction mixture may be permitted to stand for a period of time following completion of the contacting of the reactants to assure completion of the reaction. Following any such standing period, the reaction mixture is processed in conventional procedures to separate the product. As the products are typically crystalline solids which precipitate in the reaction mixture, separation is most readily carried out by filtration.

The following examples illustrate the best mode now known for the practice of the present invention and will enable those skilled in the art to practice the same.

Example 1.-3-(3phenyl-3-(phenylthio)propionyl)-4- hydroxy-G-inethyl-Z-pyrone 3Tcinnamoyl-4-hydroxy 6 methyl-2 pyrone (25.6 grams; 0.1 mole) and benzenethiol (11.0 grams; 0.1 mole) were mixed with 100 milliliters of benzene and the resulting .mixture heated slowly to a temperature of. 4050 C. Ap-

to cool. Cooling of the reaction mixture resulted in the precipitation therein of the desired 3-(3-phenyl-3-(phenylthio)propionyl) 4-hydroxy-6-methyl 2-pyrone product. The product was separated by filtration, the separated product washed with cold ethanol, and the washed product recrystallized from boiling acetone-ethanol 1:1 mixture ,4 (by weight). The product thus obtained melted at 133- 35 C. l

Other representative products of the present invention, prepared in essentially, the same procedures as thosereported in Example 1, inclpdethose identified in thefollowing examples, in which'the "symbol ,M.W. isused"as an abbreviation'foif the terrri' molecular weight, and the symbol M.P.? is used;as an abbreviationfor the term fmelting point. t "f I H Examples.230 I, i v

3 cinnamoyl 4hydro xy: 6-methyl-Z-pyrone and benzeneselenol are reacted together to yield 3-(3-'phenyl-3 (phenylseleno)-propioriyl)' i- 4 hydroxy-6 methyl-2-pyrone product, M.P. C. f

3 cinnamoyl 4-hydroxycou'i'narin and benzenethiol are reacted together to obtain 3-(3-phenyl-3- (phenylthio.)- propionyl)-4-hydroxycoumarin;' "M.P. 129-18 1 C.

3 cinnamoyl 4-hydroxy-2-pyrone-and benzenethiol are reacted togetherto yield 3-(3-phenyl-3+(phenylthio)- propionyl)-4-hydroxy 2-pyrone,'M.W. of 352.4.

3 cinnamoyl 4-hydr0xy-6-methyl-2 pyrone is reacted with o-toluenethiol to obtain 3-'( 3-phenyl-3-. (o-tolylthio) propionyl) 4 hydroxy -.6-

methyP-Z pyrone; M.P. 112115 C.

3-cinnamoyl-4-hydroxycoumarin is reacted with ptoluenethiol to obtain 3-(3-phenyl-3-(patolylthioypropionyl)-4-hydroxycoumarin, M.P.1624-C'."

3 cinnamoyl 4-hydroxy-6-phenyl-Z pyrone isreacted with o-tolneneselenol, yielding 3 (3-phenyl-3-(o-tolylseleno propionyl) -4- hydroxy 6 phenyl-2-pyrone, M.W. of

3 cinnamoyl-4-hydroxy-6-rnethyl-2-pyrone.is reacted with m-toluenethiol to obtain 3-(3-phenyl-3-(m-tolylthio)- pro pionyl -4-hydroxy-6-methy1*2 pyrone,. M.P. 68-70. C.

3 (3 (2 thienyl)acryloy1)-4ehydroxy 6-phenyl 2- pyrone is reacted with o chlorobenzenethiol to obtain 3- (3 (2 thienyl) 3-(o-chlorophenylthio)propionyl).-4 hydroxy-6-phenyl-2-pyrone, of 469.1,; I

3 cinnamoyl-4 hydroxycoumarin is reacted withpchlorobenzenethiol to yield 3 (3 .phenyl-3-(p-ch1orophenylthio)propionyl)-4-hydroxycournarin,.M.P. C.

3 cinnamoyl-4-hydroxy--methyl-Lpyrone is reacted with p-toluenethiol to yield 3;(3-phenyk3-(p-tolylthio)- propionyl)-4-hydroxy-6 -methyl-2apyrone, M.P.-.1344 C.

3 cinnamoyl-4-hydroxycournarin is .reactedwith pbromobenzenethiol to ,obtain 3 (3 phenyl 3 (p-bromophenylthio propionyl.) -4- hydr oxyc oumarin, ,M.P. 161 C.

3 cinnamoyl-4-hydroxy-6-methyb2-pyrone is reacted with p-tert-butylbenzenethiol to obtain 3-'(3-phenyl-3 (P- tert-butylphenylthio)propionyl) .4 hydroxy-6methyl-2- pyrone, M.P. 77'Z9 C.

3 (3-(p-chlorophenyl)acryloyl) 4 hydroxycoumarin is reacted with p-chlorobenzeneselenol, yielding "3; 1 (3- (pchlorophenyl) 3 ,(p-chlorophenylsel'eno)propionylI-4- hydroxycoumarin, M.W. of 5183, 1 i

3 cinnamoyl-4-hydroxycoumarin is reactedlwith ptert-butylbenzenethiol to obtain 3 (3-phenyl-3-(p-t'ertbutylphenylthio) propionyl)" 4-hydroxycoum'arin, M.P. 11929 C.

3 (3-(9-phenanthryl)acryloyl) 4-hydroxy-2-pyrone is reacted with m-bromobenzen'ethiolj yielding 3 (S-(9- phenanthryl) 3 (in br'omophenylthio)propionyl) 4 hydroxy-2-pyr'one,M.W.ot 53'1.4 1 p 3 3 2,4 dichlorophenyl)acryloyl'j t-hydroxy- 'coumarin is reacted with 'p-toluenethiol,yielding?(3 (2,4- dichlorophenyl) -"'3 0- (p 'tolylt1iio)propio'riyl)-4 hydroxy- 'coumarin, M.P. 119 2l 3 (3-(p-tolyl)acryloyl) -4 hydroxy-6-niethyl-2 pyrone is reacted with m-bromoben zeneselenol', yieldihg' '3-(3-(ptolyl) 3-(m-bromophenylseleno)-4 hyd methyl-2- pyrone product, M.'.W.'of 506.31 I

3 cinnamoyl-4-hydr0xy 6 rnethyli pyrone -is reacted with p-chlorobenzene'thiol, yielding 3 "(3 -'-phenyl 3(pchlorophenylthio) propi riyl") i ftihydroJiyQSunethyl-Zpyrone, M.P. 131 C."

3 (3 (p-methoxyphenyl)acryloyl) 4-hydroXy-6- methyl-2-pyrone is reacted with benzenethiol, yielding 3- (3 (p-rnethoxyphenyl) -3- phenylthio propionyl) -4-hyhdroxy-6-methyl-2-pyrone, M.W. of 380.5.

3 (3 (3,4 dichlorophenyl)acryloyl)-4hydroxycourmarin is reacted with p-tert-butylbenzenethiol, yielding 3-(3-(3,4-dichlorophenyl)-3-(p-tert-butyl-phenylthio)- propionyl)-4-hydroxycourmain M.P. l67-l69 C7 3 (3 (9 phenanthryl)acryloyl)-4-hydroxycournarin is reacted with p-toluenethiol, yielding 3-(3-(9-phenanthryl) 3 (p-tolylthio)propionyl)-4-hydroxycoumarin M.P. 120 C.

3 cinnamoyl 4 hydroxy-6-methyl-Z-pyrone is reacted with p-bromobenzenethiol, yielding 3-(3-phenyl-3- (p-bromophenylthio)propionyl) 4-hydroxy-6-methyl-2- pyrone, M.P. 113 C.

3 (3 (p-bromophenyl)acryloyl)-4-hydroxycoumarin is reacted with benzenethiol, yielding 3 (3-(p-bromophenyl) 3-(phenylthio)propionyl)-4-hydroxycoumarin, M.W. of 481.4.

3 (3 (2-thienyl)acryloyl)-4-hydroxycoumarin is reacted With p-toluenethiol, yielding 3-(3-(2-thienyl)-3-(ptolylthio)propionyl)-4-hydroxycoumarin, M.P. 130 C.

3 cinnamoyl 4 hydroxy-Z-pyrone is reacted with ptert-butylbenzeneselenol, yielding 3 (3 phenyl 3 (ptert-butylphenylseleno)propionyl) 4-hydroxy-2-pyrone, M.W. of 455.4.

3 (3 (m-chlorophenyl)acryloyl) 4 hydroXy-6- methyl 2 pyrone is reacted with p-chlorobenzenethiol, yielding 3 (3-(m-chlorophenyl)-3-(p-chlorophenylthio)- propionyl)-4-hydroxy-6-methyl-2-pyrone, M.P. 123-124 C.

3 (3 (m-methoxyphenyl)propionyl) 4-hydroxycoumarin is reacted with p-chlorobenzenethiol, yielding 3- (3 (m-methoxyphenyl) 3-(p-chlorophenylthio)propionyl)-4-hydroxycoumarin, M.P. 12l3 C.

3 (3-(p-tolyl)acryloyl)-4-hydroxy-6-phenyl-2-pyrone is reacted with benzenethiol, yielding 3 (3-(p-tolyl)-3- (phenylthio)prpionyl) 4 hydroxy-6-phenyl-2-pyrone, M.W. of 442.539.

3-cinnamoyl-4-hydroxycoumarin is reacted with benzeneselenol, yielding 3-(3-phenyl-3-(phenylseleno)pr0pionyl-4-hydr0xycoumarin, M.P. 115-117 C.

When one of the products of the present invention is employed as a parasiticide, the unmodified product can be utilized. However, the present invention also encornpasses the utilization of the product together with a parasiticide adjuvant. In such utilization, the product can be dispersed on a finely divided solid and the resulting preparation employed as a dust. Also, a product of the present invention, or a composition comprising a product of the present invention and a finely divided solid, can be dispersed in water with the aid of a wetting agent and the resulting aqueous suspension employed as a spray. In other procedures, a product according to the present invention can be employed as the constituent of organic liquid composition, oil-in-water or water-in-oil emulsions, or water dispersion, with or without the addition of a wetting, dispersing, or emulsifying agent.

In representative procedures, the incorporation of 0.05 percent, by weight, of 3-(3-phenyl-3-(p-bromophenylthio)propionyl)-4-hydroxy 6 methyl 2 pyrone into a standard bacteriological culture medium resulted in a modified medium which gave complete inhibition of the growth of Bacillus subtilis. The same result was obtained when employing 3-(3-(3,4-dichl0rophenyl)-3-(p-tert-butylphenylthio propionyl -4-hydroxycoumarin, when employing 3- (3- (9-phenanthryl -3- (p-tolylthio) propionyl) 4-hydroxycoumarin, and when employing 3-(3-phenyl-3- phenylseleno) propionyl) -4-hydroxycoumarin.

PREPARATION OF STARTING MATERIALS The arylselenol starting materials are prepared in accordance with known procedures. See Methoden der Organischen Chemie (Houben-Weyl), Band IX, especially pages 951-970 (Georg Thieme Varlag, Stuttgart, Germany, 1955).

We claim: 1. Compound of the formula coHtt 3HR" l 0 0 R wherein R represents sulfur or selenium; R represents a phenyl radical of the formula wherein Z represents bromo, chloro, or loweralkyl of from 1 to 4, both inclusive, carbon atoms, and n represents 0 or 1; R" represents Z-thienyl, 9-phenanthryl, phenyl, or phenyl substituted by from 1 to 2 substituents, each of which is independently bromo, chloro, methyl, or methoxy.

2. The compound of claim 1 which is 3-(3-phenyl- 3 (phenylthio) propionyl) -4-hydroxycoumarin.

3. The compound of claim 1 which is 3-(3-phenyl- 3- (p-tolylthio propionyl -4-hydroxycoumarin.

4. The compound of claim 1 which is 3-(3-phenyl- 3- (phenylseleno propionyl) -4-hydroxycoumarin.

References Cited Houben-Weyl: Methoden der Chemie, vol. IX (1955), pp. 123-4.

Migidichian: Organic Synthesis, vol. H (1957), page 876.

JAMES A. PATTEN, Primary Examiner US. Cl. X.R. 

